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Effects of repeated exposure to MDMA on 5HT1a autoreceptor function: behavioral and neurochemical responses to 8-OHDPAT

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Abstract

A consistent effect of repeated exposure to 3,4 methylenedioxymethamphetamine (MDMA) is a decrease in the tissue levels of serotonin (5-HT). A variety of behavioural and neurochemical tests were conducted to determine whether the tissue deficits were accompanied by an increased sensitivity of the 5-HT1a autoreceptor. Tests were conducted 2 weeks following MDMA exposure (four injections of 10.0 mg/kg, IP, administered at 2-h intervals in a single day). The response to the 5-HT1a agonist, 8-OHDPAT (0.003–0.5 mg/kg, SC), was assessed using lower lip retraction (LLR), hypoactivity, and 5-hydroxytryptophan (5-HTP) accumulation following decarboxylase inhibition. The 8-OHDPAT produced a dose-dependent increase in LLR and hypoactivity, but these effects were comparable for MDMA and saline pretreated groups. MDMA decreased tissue levels of 5-HT and the accumulation of 5-HTP, but these effects were not reflected in the changes in autoreceptor sensitivity. The data suggest that the decrease in tissue levels of 5-HT produced by MDMA is accompanied by a decrease in tryptophan hydroxylase activity but cannot be explained by supersensitivity of the 5-HT1a autoreceptor.

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Acknowledgments

The authors gratefully acknowledge the technical assistance of Richard Moore. These studies were funded by the Royal Society of New Zealand Marsden Fund.

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Authors and Affiliations

  1. School of Psychology, Victoria University of Wellington, P.O. Box 600, Wellington, New Zealand

    Susan Schenk, Blaine Abraham, Dane Aronsen, Joyce Colussi-Mas & Jennifer Do

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  1. Susan Schenk
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  2. Blaine Abraham
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  3. Dane Aronsen
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  4. Joyce Colussi-Mas
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  5. Jennifer Do
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Correspondence to Susan Schenk.

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Schenk, S., Abraham, B., Aronsen, D. et al. Effects of repeated exposure to MDMA on 5HT1a autoreceptor function: behavioral and neurochemical responses to 8-OHDPAT. Psychopharmacology 227, 355–361 (2013). https://doi.org/10.1007/s00213-013-2980-5

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